Acute Disseminated Encephalomyelitis Patients Research Articles

Multimodal evoked potentials are useful for the diagnosis of pediatric acute disseminated encephalomyelitis.

The application of evoked potentials (EPs) to the diagnosis of acute disseminated encephalomyelitis (ADEM ) has not been investigated in detail. The aim of this study, therefore, was to analyze the value of multimodal EPs in the early diagnosis of pediatric ADEM. This was a retrospective study in which we enrolled pediatric ADEM patients and controls (Cs) from neurology units between 2017 and 2021. We measured indices in patients using brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs), and then we analyzed their early diagnostic value in ADEM patients. The mean age of the ADEM group was 6.15 ± 3.28 years (range,1-12 years) and the male/female ratio was 2.1:1 The mean age of the Cs was 5.97 ± 3.40 years (range,1-12 years) and the male/female ratio was 1.3:1. As we used magnetic resonance imaging (MRI) as the diagnostic criterion, the sensitivity, specificity, and accuracy (κ was 0.88) of multimodal EPs were highly consistent with those of MRI; and the validity could be ranked in the following order with respect to the diagnosis of ADEM: multimodal Eps > single SEP > single VEP > single BAEP. Of 34 patients with ADEM, abnormalities in multimodal EPs were 94.12%, while abnormalities in single VEPs, BAEPs and SEPs were 70.59%,64.71%and 85.3%, respectively. We noted significant differences between single VEP/BAEPs and multimodal EPs (χ2 = 6.476/8.995,P = 0.011/0.003). The combined application of multimodal EPs was superior to BAEPs, VEPs, or SEPs alone in detecting the existence of central nerve demyelination, and we hypothesize that these modalities will be applicable in the early diagnosis of ADEM.

A retrospective study on acquired demyelinating diseases in children

Background: Acquired demyelinating diseases (ADS) соnstitute а heterogeneous grоuр of central nervous system disorders of autoimmune origin that causes significant physical and cognitive disabilities. Early recognition and prompt management causes significant improvement in acute episodes of demyelinating disorders. Methods: 33 children diagnosed with demyelinating disorders at Lokmanya Tilal municipal medical college and hospital in Mumbai were enrolled. The study was conducted between January 2013 and November 2022. Demographic data, clinical profile, CSF study, serum antibody, radiological findings were collected and results were analyzed. Statistical Data was analysed using statistical software GraphPad in Stat.V3.0. Data were presented in tables and figures whenever needed. P value <0.05 considered as significant. Results: Of 33 patients, 21 (63%) were cases of acute disseminated encephalomyelitis (ADEM), 6 (18.1%) of transverse myelitis (TM), 1 case of ADEM + TM (3%), 3 (9%) of neuromyelitis optica, 1 (3%) of Optic neuritis and 1 (3%) of multiple sclerosis. ADEM patients presented with encephalopathy and multifocal neurological deficits, 40% were MOG positive. Two patients were of multiphasic ADEM. Patients of transverse myelitis had paraparesis or quadriparesis and sensory + bladder involvement. Patients with NMO presented with bilateral visual impairment with limb weakness and bladder involvement. Steroids were the primary treatment, 3 patients (9%) required intravenous immunoglobulin (IVIG) and 1 (3%) patient received plasma exchange therapy. Conclusions: ADEM is the most common ADS. Early diagnosis and management with steroids therapy improves outcome in most of the patients. Non response to steroids warrants second line treatment options like IV Immunoglobulin (IVIG) or Therapeutic plasma exchange.

Clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis patients with MOG antibodies: a retrospective study in Hangzhou, China

BackgroundTo explore the clinical characteristics and related factors of children with acute disseminated encephalomyelitis (ADEM) with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody.MethodsA retrospective study was conducted and enrolled pediatric ADEM patients who underwent serum MOG antibody detection from May 2017 to August 2020. The patients were divided into two groups: MOG- immunoglobulin G (IgG) positive (n = 35) and MOG-IgG negative (n = 50). We analyzed the clinical characteristics of MOG-IgG-positive ADEM pediatric patients and conducted a comparative analysis between the two groups.ResultsThirty-five patients (21 males and 14 females) in the MOG-IgG-positive group with encephalopathy, multifocal neurological symptoms, and typical magnetic resonance imaging (MRI) abnormalities were enrolled. They usually had a favorable outcome, while some suffered from relapse. Compared to the MOG-IgG-negative group, MOG-IgG-positive ADEM patients had a longer disease duration (median: 10 vs. 6 days), more meningeal involvement (31.4% vs. 8%) and frontal lobe involvement (82.8% vs. 68%), higher relapse rates (14.3% vs. 2%), lower serum tumor necrosis factor (1–12.4 pg/ml, median 1.7 vs. 1–34 pg/ml, median 2.2) and interferon-gamma (1–9.4 pg/ml, median 1.3 vs. 1–64 pg/ml, median 3) (P < 0.05, respectively). Multivariate logistic regression analysis showed that the longer disease duration, meningeal involvement and frontal lobe involvement were the correlated factors of patients with ADEM with MOG antibody (P < 0.05).ConclusionsOur findings provide clinical evidence that MOG-IgG positivity is associated with longer disease duration, meningeal involvement, and frontal lobe involvement.

Encephalopathy as a prognostic factor in adults with acute disseminated encephalomyelitis following COVID-19

Numerous reports support the possible occurrence of acute disseminated encephalomyelitis (ADEM) following COVID-19. Herein, we report a case of ADEM in a 53-year-old man 2 weeks after SARS-CoV-2 infection. We reviewed the reports of adult cases of ADEM and its variant acute necrotizing hemorrhagic leukoencephalitis (ANHLE) to check for possible prognostic factors and clinical/epidemiological peculiarities. We performed a descriptive analysis of clinical and cerebrospinal fluid data. Ordinal logistic regressions were performed to check the effect of clinical variables and treatments on ADEM/ANHLE outcomes. We also compared ADEM and ANHLE patients. We identified a total of 20 ADEM (9 females, median age 53.5 years) and 23 ANHLE (11 females, median age 55 years). Encephalopathy was present in 80% of ADEM and 91.3% of ANHLE patients. We found that the absence of encephalopathy predicts a better clinical outcome in ADEM (OR 0.027, 95% CI 0.001–0.611, p = 0.023), also when correcting for the other variables (OR 0.032, 95% CI 0.001–0.995, p = 0.05). Conversely, we identified no significant prognostic factor in ANHLE patients. ANHLE patients showed a trend towards a worse clinical outcome (lower proportion of good/complete recovery, 4.5% vs 16.7%) and higher mortality (36.4% vs 11.1%) as compared to ADEM. Compared to pre-pandemic ADEM, we observed a higher median age of people with post-COVID-19 ADEM and ANHLE, a shorter interval between infection and neurological symptoms, and a worse prognosis both in terms of high morbidity and mortality. Despite being affected by the retrospective nature of the study, these observations provide new insights into ADEM/ANHLE following SARS-CoV-2 infection.

Diagnostic odyssey of acute disseminated encephalomyelitis in children

We aimed to determine whether acute disseminated encephalomyelitis (ADEM) diagnosis in children is delayed, and if so, to identify the clinical risk factors of delayed diagnosis. Standardised data were collected from children with ADEM from 2003 to 2020. Overall diagnostic delay (time between symptom onset and ADEM diagnosis), physicians’ delay (between the first medical visit and ADEM diagnosis), and patients’ delay (between symptom onset and the first medical visit) were analysed. Thirty ADEM patients were identified, including 16 (54%) with neurological deficits at discharge. Overall, physicians’, and patients’ delays were 9 (interquartile range [IQR] 6–20.5), 5.5 (IQR 3–14), and 4 (IQR 2–8) days, respectively. Overall delay was significantly associated with physicians’ delay, but not with patients’ delay. There were 61 misdiagnoses among 25 (83%) patients, while 5 (17%) were diagnosed correctly at the first visit. The misdiagnoses of common respiratory and gastrointestinal infection and aseptic meningitis were associated with overall and/or physicians’ delay. Later onset of specific neurological features suggestive of ADEM was associated with all three diagnostic delays. A unique diagnostic odyssey exists in ADEM. Several clinical risk factors were associated with the diagnostic delay.

Characteristics and Predictors of Disease Course in Children Initially Presenting with Acute Disseminated Encephalomyelitis (ADEM)

Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), characterized by new onset polyfocal neurologic symptoms with encephalopathy and multifocal demyelination, typically occurring in early childhood. The initial diagnosis of ADEM can be challenging, as up to 20% of children with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) are initially diagnosed with ADEM. Objective:To describe characteristics of patients with ADEM vs. recurrent demyelinating syndromes (MS, NMOSD, other) at the time of initial presentation and identify features at disease onset of presentations consistent with ADEM associated with monophasic demyelinating disease. Methods: This is a multicenter observational cohort study of children with a demyelinating disease diagnosis of ADEM, multiphasic ADEM, MS, and NMOSD who were followed at 12 regional pediatric MS referral centers in the US Network of Pediatric MS Centers. Descriptive statistics were used to report patient characteristics, clinical/imaging presenting features and subsequent outcomes. Logistic regression was used to predict features associated with a monophasic course. Results: As of July 2019, 872 pediatric patients with a final diagnosis of ADEM (n=89), MS (n= 664) or NMOSD (n=119) were identified. The mean +/- standard deviation follow-up for all patients was 5·7 +/- 3·1 years. ADEM patients were the youngest with mean age at first event 5·4 +/- 3·7 years (p < 0.001) and male predominance (62%) (p < 0·001). Severe clinical symptoms at onset were more frequent in ADEM (55% vs. 35% NMOSD and 15% MS, p < 0·001). After 2 years of follow-up, 78% (93/119) of patients initially diagnosed with ADEM retained this diagnosis (ADEM to ADEM), while 9·2% were later reclassified as MS, 3·3% as NMOSD and 7·5% as demyelinating disease not otherwise specified (DDNOS). In univariable logistic regression, younger age at first event was associated with retaining ADEM diagnosis, while presentation with optic neuritis and gadolinium enhancement on brain MRI were associated with ADEM reclassification to MS, NMOSD, or DDNOS at 2 years of follow-up. In multivariable analysis, older age at first event (OR 1·16 [95% CI 1·00 – 1·33] for 1-year increase, p = 0·04), presenting with optic neuritis (OR 15·31 [95% CI 3·27 – 71·66], p <0·001) and presence of gadolinium enhancement on brain MRI at onset (OR 6·80 [95% CI 2·03 – 22·78], p = 0·0019) were associated with reclassification of ADEM to MS, NMOSD or DDNOS within 2 years. Conclusion: Children who remain classified as ADEM vs. those who are reclassified as other demyelinating disorders are younger at onset, and less likely to have optic neuritis or gadolinium-enhancing lesions at disease onset. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The ethics committees of participating institutions approved this study. Parents and participants signed consent forms and assent forms when required by each center’s institutional review board prior to enrollment.

Delayed appearance of transient hyperintensity foci on T1-weighted magnetic resonance imaging in acute disseminated encephalomyelitis.

To evaluate the frequency, characteristics, and clinical significance of transient hyperintensity foci on T1-weighted images (T1WI) in acute disseminated encephalomyelitis (ADEM). Patients diagnosed with ADEM underwent MR studies at the time of disease onset and every 3months or more often thereafter. The frequency and appearance timing of abnormal signals including T1WI and their morphological characteristics were evaluated. Relations between patient symptoms and abnormal signals on MRI were also evaluated. Five ADEM patients were included in this study. Linear (n = 2) or nodular (n = 1) T1-hyperintensity foci appeared in 3 patients (60%, 3/5). Locations of T1-hyperintensity foci were both cortical/subcortical region and basal ganglia (n = 1), subcortical region alone (n = 1), and internal capsule (n = 1). Those T1-hyperintensity foci were located within the T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) hyperintensity foci on initial MRI. Some T1-hyperintensity foci also showed hyperintensity on diffusion-weighted image (DWI) and contrast enhancement. T1-hyperintensity appeared at 14-43days (median, 28days), and disappeared in 2 patients at 91days and 627days after disease onset. There were no neurological sequelae remained in any patients. T1-hyperintensity foci is not a rare finding (60%) and it can be observed after improvement in symptoms in ADEM.

Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination

BackgroundThere are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. MethodsWe reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. ResultsThe study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. ConclusionsFractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset.

Acute disseminated encephalomyelitis: prognostic value of early follow-up brain MRI.

Patients with acute disseminated encephalomyelitis (ADEM) are presumed to have radiological monophasic disease, but this is uncertain since follow-up brain MRI is not routinely performed. We aimed to ascertain combined radiological and clinical monophasic disease in ADEM patients and to assess whether performing early (<6months) follow-up brain MRI has prognostic value for subsequent multiphasic disease. We retrospectively studied the medical records of patients initially diagnosed with ADEM (years 2000-2014) at the Massachusetts General Hospital, USA. A neuroimaging specialist, masked to clinical events, reviewed all available brain MRIs. We included 62 patients (25 male; 30 pediatric; median clinical follow-up 3years) and classified them into two subgroups: (1) clinically monophasic (no new, recurrent or worsening neurological symptoms >3months after onset) (n=45), and (2) clinically multiphasic (clinical relapse >3months after onset) (n=17). All clinically monophasic patients with brain MRI follow-up (n=30) also had radiological monophasic disease a median of 2years after ADEM onset. New lesions (58 vs. 14%) and persistent lesions (100 vs. 18%) on early brain MRI [available in 40 patients (65%)], as well as clinical flares (53 vs. 20%), were more common in clinically multiphasic versus monophasic patients. These early follow-up data allowed us to predict multiphasic disease with reasonable accuracy in a multivariable model (AUC=0.73). We conclude that performing early follow-up brain MRI routinely in ADEM patients would aid clinicians in predicting multiphasic disease and may stratify patients who would benefit from initiation of disease-modifying therapy for multiple sclerosis.

Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report

BackgroundAnti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein–Barr virus (EBV) infection.Case presentationA 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative.ConclusionsThis case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers.

Clinical analysis of acute disseminated encephalomyelitis in 44 cases

Objective: To investigate the clinical features in 44 patients with acute disseminated encephalomyelitis (ADEM). Methods: Consecutive ADEM patients admitted to Neurology Department of the Third Affiliated Hospital of Sun yat-sen University during August 2009 to July 2014 were enrolled.Clinical and laboratory data of the patients were reviewed and analyzed. Results: Forty-four patients with ADEM based on the 2012 criteria were recruited, including 23 male and 21 female; 9 children, 11 teenagers and 24 adults.There were 23 monophasic ADEM (23/44, 52%) and 21 multiphasic ADEM (21/44, 48%). Fourteen patients (31.8%) had definite incentive factors within 2 weeks preceding the disease onset.The commonest presenting symptoms were fever (20/44, 45%), mental disorder (18/44, 41%), disturbance of consciousness (17/44, 39%) and seizure (12/44, 27%). The average EDSS score was (4.3±1.3), and the average mRS score was (2.7±0.9). Abnormal autoimmune antibodies were detected in 10 patients.Two patients were positive for NMO-IgG, and three patients were positive for oligoclonal bands.On MRI scanning, small lesions were observed in 18 of 44 patients (18/44, 41%); large confluent white matter lesions in 10 patients (10/44, 23%); symmetric bithalamic involvement in 12 patients (12/44, 27%). Patients were mainly treated with intravenous corticosteroids (40/44, 90.9%) and immunoglobulin G ( 13/44, 29.5%) in acute phase.Regular follow-up performed in 29 patients (65.9%), and the average follow-up time was (4.2±2.3) year.A monophasic course was found in 10 patients, and multiphasic course in 19 patients.After (2.5±2.3) years, patients with multiphasic ADEM experienced their first clinical relapse, and the relapse frequency was (3.3±1.4). The average EDSS score was (3.9±2.2), and the mRS score was (2.2±1.3) in their latest relapse.In follow-up MRI for (5.3±1.9) years, lesions in 18 patients (62.1%) were partially ameliorated, while 6 patients (20.7%) persisted, and new lesions appeared in 5 patients (17.2%). For the 13 multiphasic patients with regular treatment, intravenous corticosteroids (13/13, 100.0%) and immunoglobulin G (7/13, 53.8%) were still important treatments in the acute phase, while oral steroids (12/13, 92.3%) plus immunosuppressants including azathioprine, tacrolimus, cyclosporine and rituximab were chosen in the remission phase. Conclusions: ADEM is not uncommon in adults, presenting with multiphasic course, encephalopathy features and disseminated lesions on MRI.As it shows very heterogeneous characteristics, ADEM is best viewed as a "syndrome" rather than a specific disorder.

Impaired growth of the cerebellum in pediatric-onset acquired CNS demyelinating disease

Background: Acquired demyelinating syndromes (ADS) have the potential to negatively impact cerebellar growth, given the proclivity for infratentorial lesions in pediatric-onset multiple sclerosis (MS) and ADS. Objective: To investigate cerebellar growth longitudinally in pediatric ADS. Methods: Cerebellar volumes from 472 magnetic resonance imaging (MRI) scans of 98 patients with monophasic ADS (monoADS), monophasic acute disseminated encephalomyelitis (ADEM), and MS (49 girls; mean age: 11.4 years at first scan, mean follow-up: 3.1 years) imaged serially from onset and 897 MRI scans of 418 healthy children (223 girls, mean age: 11.3 years, mean follow-up: 2.9 years) were segmented automatically, analyzed with mixed-effect models, and compared with cerebral volume. Results: Cerebellar developmental trajectories followed a U-shaped curve, showing larger volumes in boys (p < 0.001). Cerebellar volumes in all three patient groups failed to reach age-expected trajectories, leading to significantly smaller volumes, notably in the posterior lobes. Cerebellar volume reductions were of a similar magnitude to cerebral volume reductions. Cerebellar white matter volume declined in MS and ADEM patients over time, while in monoADS patients it remained similar to controls. Cerebellar volumes did not correlate either with lesion volumes at onset or with physical disability. Conclusion: MonoADS, ADEM, and MS in childhood lead to impaired age-expected growth of the cerebellum.

Incidence of acute disseminated encephalomyelitis in the Jiangsu province of China, 2008-2011.

BackgroundIt is important to have an estimate of the incidence of acute disseminated encephalomyelitis (ADEM) because the incidence of ADEM is unknown and the outcomes undefined in China.ObjectivesThis study attempts to describe ADEM incidence in large Chinese populations located in four geographically different and moderately distant areas of the same province.MethodsA retrospective investigation was conducted with ADEM patients in Nanjing, Nantong, Yancheng and Xuzhou. The survey was carried out in regions that might have received patients meeting the case definition of ADEM provided by the International Pediatric MS Study Group from 2008 to 2011. A total of 125 hospitals were included and 412 patients were identified through the hospital information systems (HIS).ResultsThe incidence of ADEM was 0.32/100,000/year. There are two peaks on the age-specific ADEM rates curve. One is 0.77/100,000/year among 0- to 9-year-olds, the other is 0.45/100,000/year in those aged 50–59 years. The incidence rate found for ADEM in males was 0.34/100,000/year, and in females was 0.29/100,000/year. The highest incidence rate was in Nanjing (0.40/100,000/year).ConclusionsThe average annual incidence of ADEM was 0.32/100,000/year. The peak age of onset was 50–59 years old and 0–9 years old. The incidence among males was insignificantly higher than that among females. There was no significant difference in incidence by seasonal variation.

O-072 Increased Intracranial Pressure In Children With Acute Disseminated Encephalomyelitis

Introduction Lumbar puncture (LP) is routinely performed as part of the workup evaluation of suspected acute disseminated encephalomyelitis (ADEM). Mild pleocytosis and/or increased CSF protein concentration are common findings in ADEM. However, the CSF opening pressure, reflecting the intracranial pressure (ICP), has not been acknowledged to date in the literature. Methods Chart reviews of paediatric patients hospitalised in the Tel-Aviv Sourasky medical centre, between 2005–2013, that were diagnosed with ADEM, were identified retrospectively. Results Among 35 children diagnosed with ADEM, 20 who had documented CSF opening pressure comprised the study group. The mean age was 5.3 ± 4.1 years, ten males (50%); Mean CSF opening pressure was 27.8 ± 12.4 cmH 2 O, range 10–55 cmH 2 O. Considering the upper normal limit of CSF opening pressure in this age group (18 cmH 2 O), 15/20 (75%) patients had elevated pressure and one sample t-test comparison showed significant elevated CSF opening pressure among patients with ADEM (p v = 0.0023, 95% CI 3.9–15.6). Minimal pleocytosis was present in seven samples (median=2 cells/mm 2 ). Eighteen out of twenty (90%) patients had clinical complaints/signs that can be explained by increased ICP (drowsiness/encephalopathy n = 18, vomiting n = 8, headache n = 8). Discussion This study highlights that increased ICP is a prominent patho-physiologic change occurring in the CNS of ADEM patients. In our cohort, this was the most common CSF abnormal finding, independent of pleocytosis level. This observation is in line with the common non-focal neurological symptoms and signs and the beneficial effect of steroid treatment in ADEM. Furthermore, it suggests a potential efficacy of other reducing ICP treatments in ADEM.

Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis

Background: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions. Methods: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM. Results: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P=0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P=0.014). Conclusions: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM.

Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum

To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.

Cognitive and Behavioral Outcomes in Individuals With a History of Acute Disseminated Encephalomyelitis (ADEM)

We describe cognitive and behavioral outcomes in 12 males and 7 females diagnosed with acute disseminated encephalomyelitis (ADEM) in childhood. Age at assessment ranged from 6 to 23 years and all participants were at least 2 years post-ADEM presentation (mean 5.4 years). Performance was compared with 18 control subjects. Three of 19 ADEM patients met criteria for cognitive impairment, defined as performance falling ≤1.5 SD on at least three tests. Age at ADEM-onset was not associated with outcome. Despite the transient nature of the illness and absence of persistent physical disability, cognitive sequelae occur in some individuals following childhood ADEM.

Treatment of Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease, characterized by an acute onset of polyfocal central nervous system (CNS) deficits, including encephalopathy, demonstrating multifocal lesions on MRI. ADEM is typically a monophasic disorder, but recurrent and multiphasic courses have been described. Furthermore, an ADEM presentation has been reported in neuromyelitis optica (NMO) and multiple sclerosis (MS), particularly in younger children. CNS infections, other autoimmune diseases, and neurometabolic disorders may mimic ADEM at manifestation. There is no single test confirming the diagnosis of ADEM, and diagnosis is based upon a combination of clinical and radiologic features and exclusion of diseases that resemble ADEM. Therefore, a broad workup including infectious, immunologic, and metabolic tests, as well as a systematic follow-up including MRI, is indicated to establish an accurate diagnosis as a prerequisite for an optimized treatment approach. There is a lack of evidence-based, prospective clinical trial data for the management of ADEM. Empiric antibacterial and antiviral treatment is standard of care until an infectious disease process is ruled out. Based on the presumed autoimmune etiology of ADEM, the common treatment approach consists of intravenous methylprednisolone at a dosage of 20 to 30mg/kg per day (maximum 1g/day) for 3 to 5days, followed by an oral corticosteroid taper of 4 to 6weeks. In case of insufficient response or contraindications to corticosteroids, intravenous immunoglobulin G (IVIG) at a dosage of 2g/kg divided over 2 to 5days is a therapeutic option. For severe or life-threatening cases of ADEM, plasmapheresis should be considered early in the disease course. Decompressive craniectomy has been reported as a life-saving measure for ADEM patients with intracranial hypertension. There is a lack of specific recommendations for the long-term management of recurrent and multiphasic ADEM. In children with relapsing demyelinating events, the diagnosis of a chronic autoimmune CNS disease like MS or NMO should be considered.

Differentiating multiple sclerosis from other causes of demyelination using diffusion weighted imaging of the corpus callosum

To compare diffusion weighted imaging metrics in gray and white matter brain regions of patients diagnosed with multiple sclerosis (MS) to those diagnosed with secondary demyelinating diseases such as neurosarcoid and acute disseminated encephalomyelitis (ADEM). Diffusion weighted scans were performed and apparent diffusion coefficients of 12 regions of interest were determined in 30 MS patients, 21 neurosarcoid patients, and 4 ADEM patients. Mean apparent diffusion coefficients were significantly higher in MS patients than in non-MS patients in 6 of 6 of the corpus callosal regions assessed but not in any of the non-callosal white or gray matter regions assessed. Elevated apparent diffusion coefficients within the corpus callosum on diffusion weighted imaging may potentially help differentiate between patients with MS and patients with other diseases affecting the central nervous system white matter.